title: Perfluorooctane sulfonate disturbs Nanog expression through miR-490-3p in mouse embryonic stem cells.
abstract: Perfluorooctane sulfonate (PFOS) poses potential risks to reproduction and development. Mouse embryonic stem cells (mESCs) are ideal models for developmental toxicity testing of environmental contaminants in vitro. However, the mechanism by which PFOS affects early embryonic development is still unclear. In this study, mESCs were exposed to PFOS for 24 h, and then general cytotoxicity and pluripotency were evaluated. MTT assay showed that neither PFOS (0.2 µM, 2 µM, 20 µM, and 200 µM) nor control medium (0.1% DMSO) treatments affected cell viability. Furthermore, there were no significant differences in cell cycle and apoptosis between the PFOS treatment and control groups. However, we found that the mRNA and protein levels of pluripotency markers (Sox2, Nanog) in mESCs were significantly decreased following exposure to PFOS for 24 h, while there were no significant changes in the mRNA and protein levels of Oct4. Accordingly, the expression levels of miR-145 and miR-490-3p, which can regulate Sox2 and Nanog expressions were significantly increased. Chrm2, the host gene of miR-490-3p, was positively associated with miR-490-3p expression after PFOS exposure. Dual luciferase reporter assay suggests that miR-490-3p directly targets Nanog. These results suggest that PFOS can disturb the expression of pluripotency factors in mESCs, while miR-145 and miR-490-3p play key roles in modulating this effect.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China ; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Chen
authors.forename: Zhilei
authors.initials: Z
authors.lastname: Mao
authors.forename: Minjian
authors.initials: M
authors.lastname: Chen
authors.forename: Xiumei
authors.initials: X
authors.lastname: Han
authors.forename: Guizhen
authors.initials: G
authors.lastname: Du
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ji
authors.forename: Chunxin
authors.initials: C
authors.lastname: Chang
authors.forename: Virender K
authors.initials: VK
authors.lastname: Rehan
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D017738:Alkanesulfonic Acids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004785:Environmental Pollutants / Q000494:pharmacology*; D005466:Fluorocarbons / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D000071317:Nanog Homeobox Protein; D043585:Receptor, Muscarinic M2 / Q000378:metabolism
chemical_list: D017738:Alkanesulfonic Acids; D004785:Environmental Pollutants; D005466:Fluorocarbons; D018398:Homeodomain Proteins; C543499:MIRN145a microRNA, mouse; C000589011:MIRN490 microRNA, mouse; D035683:MicroRNAs; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D043585:Receptor, Muscarinic M2; C076994:perfluorooctane sulfonic acid; D000469:Alkaline Phosphatase